Agpat6 -: a novel lipid biosynthetic gene required for triacylglycerol production in mammary epithelium
Agpat6 -: a novel lipid biosynthetic gene required for triacylglycerol production in mammary epithelium
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DOI：
10.1194/jlr.m500556-jlr200
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发表时间：
2006-04-01
影响因子：
6.5
通讯作者：
Young, SG
中科院分区：
文献类型：
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作者：
Beigneux, AP;Vergnes, L;Young, SG
在BayGenomics（一种小鼠基因捕获资源）中分析突变小鼠胚胎干（ES）细胞系的序列标签时，我们发现了一种新的基因，1-酰基甘油-3-磷酸O-酰基转移酶（Agpat 6），与先前表征的甘油酯酰基转移酶具有序列相似性。Agpat 6最接近的家族成员是另一个新基因，我们暂时命名为Agpat 8。Agpat 6和Agpat 8都是从植物、线虫、苍蝇到哺乳动物的保守基因。AGPAT 6被预测含有多个跨膜螺旋，仅在哺乳动物细胞的内质网（ER）内发现。为了深入了解Agpat 6的体内重要性，我们使用来自BayGenomics的Agpat 6 ES细胞系来创建Agpat 6缺陷（gpat 6（-/-））小鼠。通过北方印迹判断，Agpat 6（-/-）小鼠缺乏全长Agpat 6转录本。Agpat 6（-/-）小鼠最引人注目的表型之一是泌乳缺陷。由Agpat 6（-/-）母亲喂养的幼崽死于围产期。通常，Agpat 6在乳腺组织的乳腺上皮中以高水平表达，但在周围的脂肪组织中不表达。组织学研究表明，Agpat 6（-/-）泌乳乳腺的腺泡和导管发育不全，乳腺上皮细胞和导管内的脂滴大小和数量急剧减少。此外，来自Agpat 6（-/-）小鼠的乳汁中的二酰基甘油和三酰基甘油显著耗尽。因此，我们确定了一种新的ER的甘油酯酰基转移酶，AGPAT 6，这是由乳腺生产乳脂的关键。- Beigneux，A. P.，L. Vergnes，X. Qiao，S.夸泰拉河戴维斯，S。M.沃特金斯河A.科尔曼河L. Walzem，M. Philips，K. Reue和S. G.年轻agpat 6-乳腺上皮细胞三酰甘油生成所需的一个新的脂质生物合成基因。
In analyzing the sequence tags for mutant mouse embryonic stem (ES) cell lines in BayGenomics (a mouse gene-trapping resource), we identified a novel gene, 1-acylglycerol-3-phosphate O-acyltransferase (Agpat6), with sequence similarities to previously characterized glycerolipid acyltransferases. Agpat6's closest family member is another novel gene that we have provisionally designated Agpat8. Both Agpat6 and Agpat8 are conserved from plants, nematodes, and flies to mammals. AGPAT6, which is predicted to contain multiple membrane-spanning helices, is found exclusively within the endoplasmic reticulum (ER) in mammalian cells. To gain insights into the in vivo importance of Agpat6, we used the Agpat6 ES cell line from BayGenomics to create Agpat6-deficient ( gpat6(-/-)) mice. Agpat6(-/-) mice lacked full-length Agpat6 transcripts, as judged by northern blots. One of the most striking phenotypes of Agpat6(-/-) mice was a defect in lactation. Pups nursed by Agpat6(-/-) mothers die perinatally. Normally, Agpat6 is expressed at high levels in the mammary epithelium of breast tissue, but not in the surrounding adipose tissue. Histological studies revealed that the aveoli and ducts of Agpat6(-/-) lactating mammary glands were underdeveloped, and there was a dramatic decrease in the size and number of lipid droplets within mammary epithelial cells and ducts. Also, the milk from Agpat6(-/-) mice was markedly depleted in diacylglycerols and triacylglycerols. Thus, we identified a novel glycerolipid acyltransferase of the ER, AGPAT6, which is crucial for the production of milk fat by the mammary gland. - Beigneux, A. P., L. Vergnes, X. Qiao, S. Quatela, R. Davis, S. M. Watkins, R. A. Coleman, R. L. Walzem, M. Philips, K. Reue, and S. G. Young. Agpat6 - a novel lipid biosynthetic gene required for triacylglycerol production in mammary epithelium.